EBV PATHOGENESIS IN HIV-ASSOCIATED HAIRY LEUKOPLAKIA

毛状白斑(HLP)是人类免疫缺陷病毒(HIV)感染者常见的机会性感染。HLP发生在舌侧，由EB病毒(EBV)引起。HLP作为生殖性EBV感染的唯一病理表现和上皮细胞EBV感染的唯一非恶性病变而引人注目。HLP提供了对EBV持续存在的机制以及特定EBV基因产物在HIV相关EBV发病机制中的作用的见解。三个假设将被检验：1)舌上皮细胞是HIV感染者持续EBV感染的第二个储存库。2)HLP是EBV潜伏期基因和产生期EBV基因共同表达的结果。3)新的分子机制调节HLP中EBV基因表达的独特模式。在一项临床研究方案中，患有HLP的HIV感染志愿者将接受抗病毒治疗，以抑制EBV复制并诱导BV潜伏期。随后停止抗病毒治疗将允许EBV重新激活。在抗病毒治疗之前、期间和之后收集舌头和血液淋巴细胞组织。分子研究将调查EBV潜伏和重新激活的分子生物学和流行病学。将探讨基因表达在EBV发病机制中的作用，包括EBV基因序列变异和基因重组在HLP中的功能后果。最后，将探讨HIV-EBV相互作用在HLP发病机制中的作用。这项研究的结果将阐明HLP中EBV致病的分子机制，适用于其他EBV相关疾病，包括鼻咽癌和HIV相关淋巴瘤。

Hairy leukoplakia (HLP) is a common opportunistic infection in human immunodeficiency virus (HIV)-infected individuals. HLP occurs on the lateral tongue and is caused by the Epstein-Barr virus (EBV). HLP is remarkable as the only pathologic manifestation of productive EBV infection and as the only non-malignant lesion of epithelial cell EBV infection. HLP offers insight into the mechanisms of EBV persistence and the role of specific EBV gene products in HIV-associated EBV pathogenesis. Three hypotheses will be tested: 1) That tongue epithelial cells are a second reservoir of persistent EBV infection in HIV-infected individuals. 2) That HLP results from a unique co-expression of both latent and productive EBV genes. 3) That novel molecular mechanisms regulate the unique pattern of EBV gene expression seen in HLP. In a clinical study protocol, HIV-infected volunteers with HLP will be treated with antiviral therapy to inhibit EBV replication and induce BV latency. Subsequent withdrawal of antiviral therapy will permit EBV reactivation. Tongue and blood lymphocyte tissues will be collected before, during, and after antiviral therapy. Molecular studies will investigate the molecular biology and epidemiology of EBV latency and reactivation. The role of gene expression in EBV pathogenesis will be investigated, including the functional consequences of EBV gene sequence variation and genetic recombination in HLP. Finally, the role of HIV-EBV interaction in HLP pathogenesis will be investigated. The results of this study will elucidate molecular mechanisms of EBV pathogenesis in HLP applicable to other EBV-associated diseases, including nasopharyngeal carcinoma and HIV-associated lymphomas.